Category: biosynthesis
Bacterial peptidoglycan is a cross-linked polymer of NAG-NAM (N-acetyl-glucosamine + N-acetyl-muramic acid) with pentapeptide cross-links forged by transpeptidase enzymes (penicillin-binding proteins, PBPs). β-lactams (penicillins, cephalosporins, carbapenems, monobactams) mimic the D-Ala-D-Ala terminus of the pentapeptide → acylate the PBP active-site serine → halt cross-linking → osmotic lysis (bactericidal in growing bacteria). β-lactamases hydrolyze the β-lactam ring; β-lactamase inhibitors (clavulanate, tazobactam, sulbactam, avibactam, vaborbactam) preserve the partner antibiotic. Vancomycin works upstream — binds the D-Ala-D-Ala terminus directly, preventing transpeptidation; resistance via D-Ala-D-Lac (VRE) or thickened cell wall (VISA).